Toll-like receptor activation regulates the paracrine effect of adipose-derived mesenchymal stem cells on reversing osteoarthritic phenotype of chondrocytes.

BACKGROUND: The therapeutic efficacy of intra-articular mesenchymal stem cells (MSCs) injection for patients with osteoarthritis (OA) currently exhibits inconsistency, and the underlying mechanism remains elusive. It has been postulated that the immunomodulatory properties and paracrine activity of MSCs might be influenced by the inflammatory micro-environment within osteoarthritic joints, potentially contributing to this observed inconsistency. METHODS: Adipose-derived MSCs (ADSCs) were isolated from SD rats and pre-treated with Toll-like receptor 3 (TLR3) agonist Poly I:C or Toll-like receptor 4 (TLR4) agonist LPS. The pre-treated ADSCs were then co-cultured with IL-1ß-induced osteoarthritic chondrocytes using a Transwell system to analyze the paracrine effect of ADSCs on reversing the osteoarthritic phenotype of chondrocytes. RESULTS: RT-PCR and Western blot analysis revealed that Poly I:C and LPS pre-treatments up-regulated the expression of IL-10 and IL-6 in ADSCs, respectively. Furthermore, only Poly I:C-preconditioned ADSCs significantly promoted proliferation while inhibiting apoptosis in IL-1ß-treated chondrocytes. Additionally, Poly I:C-preconditioned ADSCs downregulated MMP13 expression while upregulating aggrecan and collagen II expression levels in IL-1ß-treated chondrocytes. CONCLUSIONS: TLR3 activation polarizes ADSCs into an immunomodulatory phenotype distinct from TLR4 activation, exerting differential effects on reversing the osteoarthritic phenotype of chondrocytes; thus indicating that MSCs' paracrine effect regulated by TLRs signaling impacts the efficacy of intra-articular MSCs injection.

Cimetidine Attenuates Therapeutic Effect of Anti-PD-1 and Anti-PD-L1 and Modulates Tumor Microenvironment in Colon Cancer.

Histamine modulates immunity by binding to histamine receptor 2 (H2R). Cimetidine, an H2R antagonist that inhibits gastric acid secretion and treats gastrointestinal ulcers, interferes with histamine-mediated immunomodulation and may have anticancer activity. This study examined cimetidine's effect on the anticancer effect of anti-PD-L1 in colon cancer. The MTT assay, colony formation assay, and DNA histograms assessed cell viability, clonogenicity, and cell cycle distribution, respectively. Flow cytometry measured H2R and PD-L1 expression and estimated specific immune cell lineages. For the in vivo study, tumor cells were subcutaneously implanted into the right flank of BALB/c mice. Cimetidine had no significant effect on CT26 cell viability, clonogenicity, or cell cycle distribution. It also did not affect H2R and PD-L1 expression levels in CT26 cells. In vivo, anti-PD-1 and anti-PD-L1 suppressed CT26 tumor growth, whereas cimetidine showed mild antitumor activity. In the combined experiment, cimetidine significantly attenuated anti-PD-1 and anti-PD-L1' antitumor effects without major toxicity. In the tumor microenvironment, anti-PD-L1 increased CD3+ T, CD4+ T, and CD8+ T cells and M1 macrophages. Combined treatment with cimetidine reversed this. Cimetidine also reversed anti-PD-1 and anti-PD-L1's decrease in circulating and tumor-associated neutrophils. Cimetidine attenuated anti-PD-L1's antitumor effect and modulated the tumor microenvironment in colon cancer.

One-step stromal vascular fraction therapy in osteoarthritis with tropoelastin-enhanced autologous stromal vascular fraction gel.

Background: Osteoarthritis (OA) is a debilitating degenerative joint disease, leading to significant pain and disability. Despite advancements, current regenerative therapies, such as mesenchymal stem cells (MSCs), face challenges in clinical efficacy and ethical considerations. This study aimed to evaluate the therapeutic potential of stromal vascular fraction gel (SVF-gel) in comparison to available treatments like hyaluronic acid (HA) and adipose-derived stem cells (ADSCs) and to assess the enhancement of this potential by incorporating tropoelastin (TE). Methods: We conducted a comparative laboratory study, establishing an indirect co-culture system using a Transwell assay to test the effects of HA, ADSCs, SVF-gel, and TE-SVF-gel on osteoarthritic articular chondrocytes (OACs). Chondrogenic and hypertrophic markers were assessed after a 72-hour co-culture. SVF-gel was harvested from rat subcutaneous abdominal adipose tissue, with its mechanical properties characterized. Cell viability was specifically analyzed for SVF-gel and TE-SVF-gel. The in vivo therapeutic effectiveness was further investigated in a rat model of OA, examining MSCs tracking, effects on cartilage matrix synthesis, osteophyte formation, and muscle weight changes. Results: Cell viability assays revealed that TE-SVF-gel maintained higher cell survival rates than SVF-gel. In comparison to the control, HA, and ADSCs groups, SVF-gel and TE-SVF-gel significantly upregulated the expression of chondrogenic markers COL 2, SOX-9, and ACAN and downregulated the hypertrophic marker COL 10 in OACs. The TE-SVF-gel showed further improved expression of chondrogenic markers and a greater decrease in COL 10 expression compared to SVF-gel alone. Notably, the TE-SVF-gel treated group in the in vivo OA model exhibited the most MSCs on the synovial surface, superior cartilage matrix synthesis, increased COL 2 expression, and better muscle weight recovery, despite the presence of fewer stem cells than other treatments. Discussion: The findings suggest that SVF-gel, particularly when combined with TE, provides a more effective regenerative treatment for OA by enhancing the therapeutic potential of MSCs. This combination could represent an innovative strategy that overcomes limitations of current therapies, offering a new avenue for patient treatment. Further research is warranted to explore the long-term benefits and potential clinical applications of this combined approach.

A new abietane diterpenoid from Lycopodium complanatum.

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].

Effects of Visual Aids for End-of-Life Care on Decisional Capacity of People With Dementia.

Purpose This study evaluated the decision-making capacity of persons with mild and moderate dementia on end-of-life care when using visual aids. A secondary purpose was to learn whether the judges naive to the experimental conditions would rate participants' decisional abilities as better when augmented by visual aids, thereby validating the behavioral changes due to the use of these external support. Method Twenty older adults with mild and moderate dementia demonstrated Understanding, Expressing a Choice, Reasoning, and Appreciation of 2 medical vignettes under 2 counterbalanced conditions: verbal alone or verbal with visual aids. Transcripts were analyzed and scored to measure decisional skills. Twelve judges rated participants' decisional abilities using a 7-point Likert scale. Results Participants demonstrated significantly better overall decisional capacity in Understanding, Reasoning, and Appreciation when supported by visual aids during the decision-making process. No significant differences between conditions were found in Expressing a Choice, the decisional skill Logical Sequence under Reasoning, and Acknowledgment under Appreciation. Overall, the judges' ratings validated these outcomes; the judges' ratings reflected greater agreement in the visual condition than in the verbal condition. Conclusions Findings indicated that visual aids (a) improved the decision-making capacity of individuals with dementia in comprehending medical information, employing supportive reasons, and relating this information to his or her own situation and (b) contain the potential for judges who majored or are majoring in speech-language pathology to reach a stronger consensus when determining the decision-making capacity of individuals with dementia.

The role of sentinel lymph node biopsy in early-stage cervical cancer: A systematic review.

Pelvic lymphadenectomy procedure is included as part of the standard protocol of radical hysterectomy for women with early-stage cervical cancer (Stage IA to IB1). However, an important sequel to lymphadenectomy procedure is the possible occurrence of lymphedema in the lower abdomen and lower extremities. Previous researches also find that women with lymphedema experience many emotional impacts, including depression, anxiety, and adjustment problems. Only approximately 10% of women with clinical stage IB cervical carcinoma were involved with metastatic disease. If we could better define the relevant lymphatic nodes that must be removed, it is then possible to limit routinely performed lymphadenectomy for regional nodal metastasis in the pelvis, and hence reduce the need for extended surgical staging (para-aortic lymphadenectomy). We systematically reviewed a body of literature and updated available information concerning the current progress on the application of sentinel lymph node biopsy in women with early-stage cervical cancer. All detection methods (preoperative injection of radiocolloid tracer, intraoperative injection of blue dye, or a combination of both techniques) demonstrated reasonable sensitivity (with a few exceptions), high specificity, low false-negative rate and high negative predictive value. The review of the literature in this paper should convince the readers that sentinel lymph node biopsy has the potential to improve the quality of life and the possibility to maintain relapse-free survival for women with cervical cancer. The proper identification of negative sentinel lymph node allows individualized therapy and may preclude the need of lymphadenectomy procedure in most of these women.

Effects of partial replacement of fish meal by yeast hydrolysate on complement system and stress resistance in juvenile Jian carp (Cyprinus carpio var. Jian).

A 10-week feeding trial was carried out to investigate the effects of dietary fish meal replacement by yeast hydrolysate (YH) on growth performance, complement system and stress resistance of juvenile Jian carp (Cyprinus carpio var. Jian) (initial average weight 19.44 ± 0.06 g). In the study, there were five groups: one control group was fed with a basal diet (YH0), and four treatment groups were fed with dietary fish meal replaced by 1% YH (YH1), 3% (YH3), 5% (YH5) and 7% (YH7), respectively. Each group had four replicates. At the end of feeding trial, twelve fish from each group (three fish per replicate) were randomly selected for assessing the growth and immunity. Meanwhile, 20 fish per replicate were injected by Aeromonas hydrophila. The results showed that (1) Replacement levels of YH significantly affected the growth of the fish with the highest values of weight gain (WG) occurred in fish fed YH3 diet. However, no significant difference in feed conversion ratios (FCR) was observed among all groups. (2) Pre-stressed plasma lysozyme activity, total protein and albumin contents and complement component 3 (C3) and complement component 4 (C4) levels of fish fed YH3 diet were significantly higher than those of fish fed YH0 diet. However, post-stressed immune parameters of fish in all groups were significantly lower. (3) There was a trend that the expression levels of the complement-related genes (c1r/s-A, c4-1, c3-H1, c5-1, fb/c2-A, mbl-2 and masp) initially increased and then decreased except mbl-2 and masp, with the maximum values observed in fish fed YH3 diet. Before stress, the expression levels of the inflammation-related genes (alp, il-1ß and tnf-α) in the hepatopancreas and spleen of fish fed YH1 diet and YH7 diet were significant higher than that of fish fed YH0 diet. After stress, no significant difference in the expression levels of those genes was observed among all groups. These results indicated that FM replacement by YH could improve growth performance, enhance innate immunity, and activate complement via the alternative complement pathway (ACP) and the classical complement pathway (CCP).

Efficacy of Voice Therapy for Patients With Early Unilateral Adductor Vocal Fold Paralysis.

OBJECTIVES: Although a variety of therapeutic techniques have been suggested for patients with unilateral adductor vocal fold paralysis (UAVFP), they were not aimed specifically at determining the efficacy of early intervention for these patients. The purposes of this study are to explore a protocol of voice therapy and to investigate its efficacy in voice therapy for patients with early UAVFP. A 12-week planned voice therapy protocol, including vocal function exercise, hard attack, and resonance voice therapy, was given to 10 patients within 6 months of initial diagnosis. Additionally, nine patients diagnosed with UAVFP within 6 months served as controls. METHODS: Multidimensional evaluations of voice function were obtained for statistical analyses. RESULTS: Compared to a control group, the experimental group receiving voice therapy exhibited significant improvement in the following: (1) glottal closure; (2) voice quality of grade, breathiness, monotone, and resonance; (3) acoustic measurements of jitter, shimmer, and noise-to-harmonic ratio; (4) aerodynamics measurements of maximum phonation time, phonation threshold pressure, and phonation quotient; and (5) Voice Handicap Index of functional subscale. CONCLUSION: This prospective study established an effective protocol of early intervention of voice therapy in patients with UAVFP and demonstrated its efficacy in data on laryngeal physiology, voice quality, voice stability, voice efficiency, and communication function.

Extensor Tendon Splitting Simplified Technique for Treating the Dislocation of the Index Metacarpophalangeal Joint: A Case Report / 대한정형외과학회잡지

Dislocation of index metacarpophalangeal joint is complex and usually cannot be reduced by closed method. It is a relatively rare injury and there are no widely published studies on its management. We have experienced a case combined with osteochondral fracture of the dorsoulnar aspect of metacarpal head and reduced it using extensor tendon splitting simplified technique with good results. This technique is seemed te be simpler and safer than volar approach described by Kaplan.

Radical Surgical Treatment of Thoracic Spinal Tuberculosis by Extrapleural Approach / 대한정형외과학회잡지

A total 12 cases of tuberculous spondylitis of thoracic spine had been treated by anterior decompression and interbody fusion through extrapleural approach from March, 1979 to June, 1980. In this study, six impending or complete paraplegics were included. Prognosis of paraplegia depends on its grade, duration and local pathology. Extrapleural approach seems to offer the following advantages over all the other ones; lesser risk, no Iimitation of surgical fleid, less chance of contaminating pleural cavity, less postoperative complications, especially indicated for the elderly paraplegics of Incomplete or complete type and less cumbersome Immediate postoperative care.